{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:36:14Z","timestamp":1789569374385,"version":"build-2803163510"},"reference-count":109,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged as one of the most promising advances in cancer treatment, having successfully demonstrated its efficacy in haematological malignancies. However, in solid tumours, such as colon cancer, it is proving difficult to achieve the same results due to the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment. To address these challenges in CRC, new approaches are proposed, including combined therapies, the regional administration of CAR-T cells and more complex CAR structures, among others. This review comprehensively summarises the current landscape of CAR-T cell therapy in CRC from the potential tumour targets to the preclinical studies and clinical trials, as well as the limitations and future perspectives of this novel antitumour strategy.<\/jats:p>","DOI":"10.3390\/ijms222111781","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8692-6482","authenticated-orcid":false,"given":"Cristina","family":"Aparicio","sequence":"first","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Belver","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-5245","authenticated-orcid":false,"given":"Luc\u00eda","family":"Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Espeso","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-8756","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-6675","authenticated-orcid":false,"given":"Margarita","family":"Gonz\u00e1lez-Vallinas","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.24265\/horizmed.2018.v18n3.11","article-title":"Inmunolog\u00eda del c\u00e1ncer I: Bases moleculares y celulares de la respuesta inmune antitumoral","volume":"18","author":"Pareja","year":"2018","journal-title":"Horiz. M\u00e9dico"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2478\/ahp-2020-0002","article-title":"A brief history of CAR-T cells: From laboratory to the bedside","volume":"51","year":"2020","journal-title":"Acta Haematol. Pol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_6","first-page":"9918116","article-title":"Colorectal cancer: From genetic landscape to targeted therapy","volume":"2021","author":"Bakkach","year":"2021","journal-title":"J. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1056\/NEJMra0804588","article-title":"Molecular origins of cancer: Molecular basis of colorectal cancer","volume":"361","author":"Markowitz","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12094-018-02002-w","article-title":"SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018)","volume":"21","author":"Gallego","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_9","first-page":"89","article-title":"Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors","volume":"14","author":"Prashanth","year":"2019","journal-title":"Prz. Gastroenterol."},{"key":"ref_10","first-page":"476","article-title":"Drug Therapy: Systemic therapy for colorectal cancer","volume":"352","author":"Meyerhardt","year":"2005","journal-title":"Arch. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1053\/j.gastro.2008.02.098","article-title":"Systemic treatment of colorectal cancer","volume":"134","author":"Wolpin","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.3390\/cancers3033279","article-title":"Assessment of the evolution of cancer treatment therapies","volume":"3","author":"Arruebo","year":"2011","journal-title":"Cancers"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature10673","article-title":"Cancer immunotherapy comes of age","volume":"480","author":"Mellman","year":"2011","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1002\/jcp.24886","article-title":"Generation of tumor-specific cytotoxic T-lymphocytes from the peripheral blood of colorectal cancer patients for adoptive T-cell transfer","volume":"230","author":"Carluccio","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1002\/ijc.31285","article-title":"Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer","volume":"142","author":"Ishikawa","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_16","first-page":"864","article-title":"Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing \u03b1-gal epitopes","volume":"18","author":"Xing","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s13277-013-1096-1","article-title":"The phenotype of ex vivo generated cytokine-induced killer cells is associated with overall survival in patients with cancer","volume":"35","author":"Pan","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pan, Q.Z., Zhao, J.J., Yang, C.P., Zhou, Y.Q., Lin, J.Z., Tang, Y., Gu, J.M., Wang, Q.J., Li, Y.Q., and He, J. (2020). Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection. Oncoimmunology, 9.","DOI":"10.1080\/2162402X.2020.1752563"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.biopha.2014.07.010","article-title":"Effects of cytokine-induced killer cell treatment in colorectal cancer patients: A retrospective study","volume":"68","author":"Zhang","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.clcc.2016.02.005","article-title":"Autologous Cytokine-Induced Killer Cells improves overall survival of metastatic colorectal cancer patients: Results from a phase II clinical trial","volume":"15","author":"Zhao","year":"2016","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12957-017-1278-1","article-title":"Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment","volume":"15","author":"Xie","year":"2017","journal-title":"World J. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1155\/2014\/603871","article-title":"Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine-induced killer cell therapy","volume":"2014","author":"Zhu","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_23","first-page":"1","article-title":"Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients","volume":"9","author":"Gao","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/sj.gt.3302608","article-title":"Dendritic cell therapy with interferon-\u03b1 synergistically suppresses outgrowth of established tumors in a murine colorectal cancer model","volume":"13","author":"Ishii","year":"2006","journal-title":"Gene Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0157830","article-title":"Combination of NK cells and cetuximab to enhance anti-tumor responses in RAS mutant metastatic colorectal cancer","volume":"11","author":"Veluchamy","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.3892\/ol.2016.4835","article-title":"Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model","volume":"12","author":"Chen","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00087","article-title":"In Vivo efficacy of umbilical cord blood stem cell-derived NK cells in the treatment of metastatic colorectal cancer","volume":"8","author":"Veluchamy","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jcyt.2017.09.009","article-title":"Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma","volume":"20","author":"Li","year":"2018","journal-title":"Cytotherapy"},{"key":"ref_29","first-page":"3741","article-title":"Adoptive chemoimmunotherapy using activated \u03b1\u03b2 T cells for stage IV colorectal cancer","volume":"36","author":"Yoshida","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1158\/1078-0432.CCR-08-1638","article-title":"Characterization of genetically modified T-cell receptors that recognize the CEA:691-699 peptide in the context of HLA-A2.1 on human colorectal cancer cells","volume":"15","author":"Parkhust","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40364-017-0102-y","article-title":"Engineering CAR-T cells","volume":"5","author":"Zhang","year":"2017","journal-title":"Biomark. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.3389\/fimmu.2018.02940","article-title":"Overcoming target driven fratricide for T cell therapy","volume":"9","author":"Breman","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrc.2016.97","article-title":"Engineered T cells: The promise and challenges of cancer immunotherapy","volume":"16","author":"Fesnak","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.omtm.2018.12.009","article-title":"Engineering and design of chimeric antigen receptors","volume":"12","author":"Guedan","year":"2019","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: From T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1517\/14712598.2015.1046430","article-title":"TRUCKs: The fourth generation of CARs","volume":"15","author":"Chmielewski","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"D\u2019Aloia, M.M., Zizzari, I.G., Sacchetti, B., Pierelli, L., and Alimandi, M. (2018). CAR-T cells: The long and winding road to solid tumors. Cell Death Dis., 9.","DOI":"10.1038\/s41419-018-0278-6"},{"key":"ref_38","unstructured":"(2021, September 21). ClinicalTrials.gov (term search: CAR-T), Available online: https:\/\/clinicaltrials.gov\/ct2\/results?term=car-t."},{"key":"ref_39","first-page":"194","article-title":"Immunotherapy of cancer","volume":"46","author":"Trapani","year":"2017","journal-title":"Aust. Fam. Physician"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.3748\/wjg.v24.i48.5418","article-title":"Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens","volume":"24","author":"Wagner","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.canlet.2020.10.040","article-title":"T-cell-based immunotherapy in colorectal cancer","volume":"498","author":"Feng","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bakarurraini, N.A.A.R., Mutalib, N.S.A., Jamal, R., and Abu, N. (2020). The landscape of tumor-specific antigens in colorectal cancer. Vaccines, 8.","DOI":"10.3390\/vaccines8030371"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1007\/s10637-020-00955-w","article-title":"The old CEACAMs find their new role in tumor immunotherapy","volume":"38","author":"Han","year":"2020","journal-title":"Invest. New Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.ymthe.2017.03.010","article-title":"Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+ Metastatic Colorectal Cancers","volume":"25","author":"Zhang","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.2147\/CMAR.S253369","article-title":"Biochemical markers of colorectal cancer\u2013present and future","volume":"12","author":"Jelski","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/23808993.2021.1876518","article-title":"GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer","volume":"6","author":"Lisby","year":"2021","journal-title":"Expert Rev. Precis. Med. Drug Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1227897","DOI":"10.1080\/2162402X.2016.1227897","article-title":"GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity","volume":"5","author":"Magee","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1158\/2326-6066.CIR-16-0362","article-title":"Human GUCY2C-targeted chimeric antigen receptor (CAR)-expresssing T cells eliminate colorectal cancer metastases","volume":"6","author":"Magee","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zingoni, A., Molfetta, R., Fionda, C., Soriani, A., Paolini, R., Cippitelli, M., Cerboni, C., and Santoni, A. (2018). NKG2D and its ligands: \u201cOne for all, all for one\u201d. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00476"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1158\/2326-6066.CIR-15-0098","article-title":"NKG2D receptor and its ligands in host defense","volume":"3","author":"Lanier","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.coi.2018.02.004","article-title":"NKG2D and its ligands in cancer","volume":"51","author":"Dhar","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2174\/1568026620666200303123102","article-title":"Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors","volume":"20","author":"Sabbah","year":"2020","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_54","first-page":"1","article-title":"MiR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy","volume":"11","author":"Huang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/annonc\/mdy100","article-title":"Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer","volume":"29","author":"Siena","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15065","DOI":"10.18632\/oncotarget.3527","article-title":"HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer","volume":"6","author":"Styczen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.canlet.2018.06.040","article-title":"Extracellular domain of EpCAM enhances tumor progression through EGFR signaling in colon cancer cells","volume":"433","author":"Liang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"857","DOI":"10.2174\/1568009618666180102102311","article-title":"Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update","volume":"18","author":"Eyvazi","year":"2018","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s10555-020-09898-3","article-title":"Expression and function of epithelial cell adhesion molecule EpCAM: Where are we after 40 years?","volume":"39","author":"Gires","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.prp.2018.10.024","article-title":"The prognostic role of tumor associated glycoprotein 72 (TAG-72) in stage II and III colorectal adenocarcinoma","volume":"215","author":"Cho","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1080\/14712598.2021.1843628","article-title":"Mesothelin-targeted CAR-T cell therapy for solid tumors","volume":"21","author":"Klampatsa","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_62","first-page":"1741","article-title":"Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer","volume":"19","author":"Inoue","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/med.21462","article-title":"Anti-MUC1 aptamer: A potential opportunity for cancer treatment","volume":"37","author":"Nabavinia","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_64","first-page":"1765","article-title":"PLAP -CAR T cells mediate high specific cytotoxicity against colon cancer cells","volume":"25","author":"Li","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Reiswich, V., Gorbokon, N., Luebke, A.M., Burandt, E., Menz, A., Kluth, M., Hube-Magg, C., Wittmer, C., Weidemann, S., and Fraune, C. (2021). Pattern of placental alkaline phosphatase (PLAP) expression in human tumors: A tissue microarray study on 12,381 tumors. J. Pathol. Clin. Res.","DOI":"10.1002\/cjp2.237"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/cbin.11243","article-title":"CD133: An emerging prognostic factor and therapeutic target in colorectal cancer","volume":"44","author":"Akbari","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8192","DOI":"10.1002\/jcp.27619","article-title":"The most reliable surface marker for the identification of colorectal cancer stem-like cells: A systematic review and meta-analysis","volume":"234","author":"Abbasian","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.clcc.2018.02.013","article-title":"c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival","volume":"17","author":"Lee","year":"2018","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Safaie Qamsari, E., Safaei Ghaderi, S., Zarei, B., Dorostkar, R., Bagheri, S., Jadidi-Niaragh, F., Somi, M.H., and Yousefi, M. (2017). The c-Met receptor: Implication for targeted therapies in colorectal cancer. Tumour Biol., 39.","DOI":"10.1177\/1010428317699118"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1536012118776068","article-title":"PSMA Theranostics: Current Status and Future Directions","volume":"17","author":"Rahbar","year":"2018","journal-title":"Mol. Imaging"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.2967\/jnumed.119.233312","article-title":"PET imaging quantifying 68Ga-PSMA-11 uptake in metastatic colorectal cancer","volume":"61","author":"Cuda","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13545","DOI":"10.18632\/oncotarget.14592","article-title":"Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis","volume":"8","author":"Ang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1002\/cam4.2361","article-title":"Significantly increased anti-tumor activity of carcinoembryonic antigen-specific chimeric antigen receptor T cells in combination with recombinant human IL-12","volume":"8","author":"Chi","year":"2019","journal-title":"Cancer Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1089\/hum.2018.229","article-title":"Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer","volume":"30","author":"Zhang","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_75","first-page":"945","article-title":"Antitumor activity of NKG2D CAR-T cell against human colorectal cancer cells in vitro and in vivo","volume":"9","author":"Deng","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.ymthe.2018.09.009","article-title":"In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin\u2019s Lymphomas","volume":"26","author":"Ramos","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.ymthe.2019.06.007","article-title":"Blocking CD30 on T Cells by a Dual Specific CAR for CD30 and Colon Cancer Antigens Improves the CAR T Cell Response against CD30\u2212 Tumors","volume":"27","author":"Hombach","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/CJI.0000000000000251","article-title":"Chimeric antigen receptor-modified T cells repressed solid tumors and their relapse in an established patient-derived colon carcinoma xenograft model","volume":"42","author":"Teng","year":"2019","journal-title":"J. Immunother."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hombach, A.A., Geumann, U., G\u00fcnther, C., Hermann, F.G., and Abken, H. (2020). IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells. Cells, 9.","DOI":"10.3390\/cells9040873"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Sureban, S.M., Berahovich, R., Zhou, H., Xu, S., Wu, L., Ding, K., May, R., Qu, D., Bannerman-menson, E., and Golubovskaya, V. (2020). DCLK1 Monoclonal Antibody-Based CAR-T Cells Asa Novel Treatment Strategy against Human Colorectal Cancers. Cancers, 12.","DOI":"10.3390\/cancers12010054"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/cgt.2016.14","article-title":"Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery","volume":"23","author":"Katz","year":"2016","journal-title":"Cancer Gene Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.omto.2021.02.013","article-title":"The antitumor capacity of mesothelin-CAR-T cells in targeting solid tumors in mice","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.3748\/wjg.v26.i13.1394","article-title":"Mouse models of colorectal cancer: Past, present and future perspectives","volume":"26","author":"Mullins","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/2162402X.2018.1440169","article-title":"CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial","volume":"7","author":"Wang","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-016-0378-7","article-title":"Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma","volume":"10","author":"Feng","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_86","first-page":"2355","article-title":"Construction of chimeric antigen receptor-modified T cells targeting EpCAM and assessment of their anti-tumor effect on cancer cells","volume":"20","author":"Zhou","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.omto.2020.04.013","article-title":"Electroporation of NKG2D RNA CAR Improves V\u03b39V\u03b42 T Cell Responses against Human Solid Tumor Xenografts","volume":"17","author":"Ang","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/CJI.0000000000000260","article-title":"Pilot trial of adoptive transfer of chimeric antigen receptor-Transduced T cells targeting EGFRvIII in patients with glioblastoma","volume":"42","author":"Goff","year":"2019","journal-title":"J. Immunother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1158\/1078-0432.CCR-13-0709","article-title":"EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss","volume":"20","author":"Sampson","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41417-019-0104-z","article-title":"HITM-SIR: Phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA+ liver metastases","volume":"27","author":"Katz","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jitc-2020-001097","article-title":"HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery","volume":"8","author":"Katz","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Lichtenstern, C.R., Ngu, R.K., Shalapour, S., and Karin, M. (2020). Immunotherapy, Inflammation and Colorectal Cancer. Cells, 9.","DOI":"10.3390\/cells9030618"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.3389\/fimmu.2020.01965","article-title":"Use of Cell and Genome Modification Technologies to Generate Improved \u201cOff-the-Shelf\u201d CAR T and CAR NK Cells","volume":"11","author":"Morgan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"CT129","DOI":"10.1158\/1538-7445.AM2018-CT129","article-title":"Abstract CT129: The THINK clinical trial: Preliminary evidence of clinical activity of NKG2D chimeric antigen receptor T cell therapy (CYAD-01) in acute myeloid leukemia","volume":"78","author":"Sallman","year":"2018","journal-title":"Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-019-0051-2","article-title":"\u2018Off-the-shelf\u2019 allogeneic CAR T cells: Development and challenges","volume":"19","author":"Depil","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Yazdanifar, M., Barbarito, G., Bertaina, A., and Airoldi, I. (2020). \u03b3\u03b4 T Cells: The Ideal Tool for Cancer Immunotherapy. Cells, 9.","DOI":"10.3390\/cells9051305"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1200\/JCO.2021.39.3_suppl.74","article-title":"Updated data from alloSHRINK phase I first-in-human study evaluating CYAD-101, an innovative non-gene edited allogeneic CAR-T in mCRC","volume":"39","author":"Prenen","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/2162402X.2020.1846926","article-title":"Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: A single-arm, open-label, phase II trial","volume":"9","author":"Dai","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"CT123","DOI":"10.1158\/1538-7445.AM2018-CT123","article-title":"Van Den Canon, J.-L.; Carrasco, J.; Verma, B.; et al. Abstract CT123: A phase I study assessing the safety and clinical activity of multiple doses of a NKG2D-based CAR-T therapy, CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with potentially resectable liver metastases","volume":"78","author":"Lonez","year":"2018","journal-title":"Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"CT134","DOI":"10.1158\/1538-7445.AM2018-CT134","article-title":"Abstract CT134: A phase I study assessing the safety and clinical activity of multiple hepatic transarterial administrations of a NKG2D-based CAR-T therapy CYAD-01, in patients with unresectable liver metastases from colorectal cancer","volume":"78","author":"Braun","year":"2018","journal-title":"Cancer Res."},{"key":"ref_101","unstructured":"(2021, September 16). Definition of Autologous NKG2D CAR T Cells KD-025-NCI Drug Dictionary-National Cancer Institute, Available online: https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer-drug\/def\/autologous-nkg2d-car-t-cells-kd-025."},{"key":"ref_102","unstructured":"(2021, September 16). Definition of Autologous Universal CAR-Expressing T Lymphocytes UniCAR02-T-NCI Drug Dictionary-National Cancer Institute, Available online: https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer-drug\/def\/autologous-universal-car-expressing-t-lymphocytes-unicar02-t."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sur, D., Havasi, A., Cainap, C., Samasca, G., Burz, C., Balacescu, O., Lupan, I., Deleanu, D., and Irimie, A. (2020). Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010182"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.canlet.2019.05.017","article-title":"Targeting the tumour immune microenvironment for cancer therapy in human gastrointestinal malignancies","volume":"458","author":"Zhang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1182\/blood.V99.9.3179","article-title":"Adapting a transforming growth factor \u03b2-related tumor protection strategy to enhance antitumor immunity","volume":"99","author":"Bollard","year":"2002","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/eji.1830260620","article-title":"Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity","volume":"26","author":"Kono","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/mt.2014.47","article-title":"Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine Receptor","volume":"22","author":"Leen","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12896-020-00623-0","article-title":"Colorectal cysts as a validating tool for CAR therapy","volume":"20","author":"Dillard","year":"2020","journal-title":"BMC Biotechnol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","article-title":"Top 10 Challenges in Cancer Immunotherapy","volume":"52","author":"Hegde","year":"2020","journal-title":"Immunity"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11781\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:18Z","timestamp":1760167398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,29]]},"references-count":109,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111781"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111781","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,29]]}}}